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Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes
Oxidative stress mediated clustering of membrane protein band 3 plays an essential role in the clearance of damaged and aged red blood cells (RBCs) from the circulation. While a number of previous experimental studies have observed changes in band 3 distribution after oxidative treatment, the detail...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457884/ https://www.ncbi.nlm.nih.gov/pubmed/26046580 http://dx.doi.org/10.1371/journal.pcbi.1004210 |
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author | Shimo, Hanae Arjunan, Satya Nanda Vel Machiyama, Hiroaki Nishino, Taiko Suematsu, Makoto Fujita, Hideaki Tomita, Masaru Takahashi, Koichi |
author_facet | Shimo, Hanae Arjunan, Satya Nanda Vel Machiyama, Hiroaki Nishino, Taiko Suematsu, Makoto Fujita, Hideaki Tomita, Masaru Takahashi, Koichi |
author_sort | Shimo, Hanae |
collection | PubMed |
description | Oxidative stress mediated clustering of membrane protein band 3 plays an essential role in the clearance of damaged and aged red blood cells (RBCs) from the circulation. While a number of previous experimental studies have observed changes in band 3 distribution after oxidative treatment, the details of how these clusters are formed and how their properties change under different conditions have remained poorly understood. To address these issues, a framework that enables the simultaneous monitoring of the temporal and spatial changes following oxidation is needed. In this study, we established a novel simulation strategy that incorporates deterministic and stochastic reactions with particle reaction-diffusion processes, to model band 3 cluster formation at single molecule resolution. By integrating a kinetic model of RBC antioxidant metabolism with a model of band 3 diffusion, we developed a model that reproduces the time-dependent changes of glutathione and clustered band 3 levels, as well as band 3 distribution during oxidative treatment, observed in prior studies. We predicted that cluster formation is largely dependent on fast reverse reaction rates, strong affinity between clustering molecules, and irreversible hemichrome binding. We further predicted that under repeated oxidative perturbations, clusters tended to progressively grow and shift towards an irreversible state. Application of our model to simulate oxidation in RBCs with cytoskeletal deficiency also suggested that oxidation leads to more enhanced clustering compared to healthy RBCs. Taken together, our model enables the prediction of band 3 spatio-temporal profiles under various situations, thus providing valuable insights to potentially aid understanding mechanisms for removing senescent and premature RBCs. |
format | Online Article Text |
id | pubmed-4457884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44578842015-06-09 Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes Shimo, Hanae Arjunan, Satya Nanda Vel Machiyama, Hiroaki Nishino, Taiko Suematsu, Makoto Fujita, Hideaki Tomita, Masaru Takahashi, Koichi PLoS Comput Biol Research Article Oxidative stress mediated clustering of membrane protein band 3 plays an essential role in the clearance of damaged and aged red blood cells (RBCs) from the circulation. While a number of previous experimental studies have observed changes in band 3 distribution after oxidative treatment, the details of how these clusters are formed and how their properties change under different conditions have remained poorly understood. To address these issues, a framework that enables the simultaneous monitoring of the temporal and spatial changes following oxidation is needed. In this study, we established a novel simulation strategy that incorporates deterministic and stochastic reactions with particle reaction-diffusion processes, to model band 3 cluster formation at single molecule resolution. By integrating a kinetic model of RBC antioxidant metabolism with a model of band 3 diffusion, we developed a model that reproduces the time-dependent changes of glutathione and clustered band 3 levels, as well as band 3 distribution during oxidative treatment, observed in prior studies. We predicted that cluster formation is largely dependent on fast reverse reaction rates, strong affinity between clustering molecules, and irreversible hemichrome binding. We further predicted that under repeated oxidative perturbations, clusters tended to progressively grow and shift towards an irreversible state. Application of our model to simulate oxidation in RBCs with cytoskeletal deficiency also suggested that oxidation leads to more enhanced clustering compared to healthy RBCs. Taken together, our model enables the prediction of band 3 spatio-temporal profiles under various situations, thus providing valuable insights to potentially aid understanding mechanisms for removing senescent and premature RBCs. Public Library of Science 2015-06-05 /pmc/articles/PMC4457884/ /pubmed/26046580 http://dx.doi.org/10.1371/journal.pcbi.1004210 Text en © 2015 Shimo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Shimo, Hanae Arjunan, Satya Nanda Vel Machiyama, Hiroaki Nishino, Taiko Suematsu, Makoto Fujita, Hideaki Tomita, Masaru Takahashi, Koichi Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes |
title | Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes |
title_full | Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes |
title_fullStr | Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes |
title_full_unstemmed | Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes |
title_short | Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes |
title_sort | particle simulation of oxidation induced band 3 clustering in human erythrocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457884/ https://www.ncbi.nlm.nih.gov/pubmed/26046580 http://dx.doi.org/10.1371/journal.pcbi.1004210 |
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